In November 1836, the Bent brothers and Ceran St. Vrain received a license authorizing them to trade on the South Platte. Construction began in 1837 on the trading post, which was to be the largest and most enduring along the river. The main business at Fort Lookout, as it was first named, was trading trinkets and beads for buffalo hides and tongues and beaver pelts, as well as accommodating passing mountain men. Fort Lookout was renamed Fort George in honor of George Bent, one of the Bent Brothers; however, this fort was generally known as St. Vrain's Fort or Fort St. Vrain.

Fort St. Vrain was located one mile north of St. Vrain Creek on the east side of the South Platte River, on the "Trapper's" or Taos Trail, which ran from Fort Taos, New Mexico, past Bent's Fort in Colorado to Fort Laramie in Wyoming. Fort St. Vrain was said to be exactly halfway between Bent's Fort and Fort Laramie and was located just a little north of its major competitors, Fort Vasquez and Fort Lupton.

Fort St. Vrain was constructed in the likeness of Bent's Fort, which was located on the Arkansas River near present day La Junta, Colorado. Exclusive of the bastions, the total length of Fort St. Vrain proper was 125 feet north to south and the total width was 75 feet. The front looked nearly straight east. There were two bastions, one on the southwest and one on the northeast corners. The walls were made of adobe bricks and were about 2 feet thick and 14 feet high. The main entrance was guarded by heavy gates and, above, by a tower. The interior of the court was surrounded by houses one story high. There was a corral inside for the cattle and horses and a cistern, lined with lime, near the southwest bastion.

Marcellin St. Vrain, Ceran's younger brother, was appointed to manage the fort for the Bent & St. Vrain Company. He worked to protect the Bent brothers' interests and lure business away from the other tading posts. To this end, he was quite successful. Fort Jackson was the first to capitulate under the Bent's power; it was sold to Bent and Company in 1838. Fort Vasquez was the next to close its doors in 1842.

During the years it operated as a trading post, St. Vrain's Fort served as a waystation and provisioning point for travelers. John C. Fremont stopped there June 10, 1842, during his first expedition, to obtain horses and coffee. In this party were 21 men, mostly from St. Louis, including 12-year-old Randolph Benton, son of Thomas H. Benton. Kit Carson was their guide. Fremont also stopped at the fort in July, 1843, during his second expedition.

Richard L. "Uncle Dick" Wooten ran the first courier service between St. Vrain's Fort, Bent's Fort and Fort Laramie in 1842. The charge for this service was $5 per half ounce plus regular government postage. It has been suggested that this was the first Pony Express of the Rocky Mountain region.

In 1844, Fort Lupton was the last fort to close under the Bent's pressure. With Fort St. Vrain's mission accomplished and with the rapid decline of the fur trade, the Bent & St. Vrain Company ended its operation of the fort in 1845. However, Marcellin stayed on for several years, at least part time, and continued with operations of the fort on his own. In 1848 Marcellin moved back to the St. Louis area. However, this was by no means the end of Fort St. Vrain. There are indications that the fort was fixed up and used to supply the prospectors of the 1849 gold rush.

George Grinnell writes that in the summer of 1854 "...Walking Coyote with War Bonnet rode up to St. Vrain's Fort. White Horse was living in a camp of Cheyennes there...and [he] saw White Horse and his wife...sitting on a bench in the hall of the fort. When the two saw Walking Coyote, they arose and walked toward the hands' messroom..." [Grinnell, George Bird. The Cheyenne Indians Their History and Ways of Life, Vol. 1. Lincoln, NE: University of Nebraska Press, Oct. 1972.] So, it would seem that the fort was still in use in the mid-1850's, at least as a residence if not a military post.

By the late 1850s, St. Vrain's Fort was fast becoming a ruins but was still holding it's own as a focal point and landmark for the early settlers. Ranchers lived around the deteriorating fort and used it as a corral. In 1859, the St. Vrain Claims Club was formed by the settlers along the South Platte to protect their land claims from claim jumpers. William N. Byers moved at the first meeting that each claimant be entitled to 160 acres, etc . . . and that "the jurisdiction of this club be coextensive with the county of St. Vrain, to embrace not less than 24 miles square, with the Town of St. Vrain, near the centre. . ."

Post offices were established at Fort St. Vrain and Fort Lupton in 1859. When Weld County (one of the original 17 counties of the Colorado Territory) was organized in 1861, the town of St. Vrain was designated the County Seat and a log courthouse was built. Unfortunately, the town did not flourish and the County Seat was moved to the Latham Stage Station, located in present day Greeley, in the mid 1860s. The original log courthouse has been preserved and moved to the historic "Centennial Village Museum" in Greeley where it may currently be viewed.

In 1911, the Centennial State Chapter (Greeley) Daughters of the American Revolution erected a monument at the site of the original fort. Mary St. Vrain Sopris, Marcellin St. Vrain's daughter, was an honored participant at the dedication ceremony. Mary was born at the fort on March 10, 1848.